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Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate underlies agmatine-induced suppression of N-type Ca2+ channel in rat celiac ganglion neurons.

Authors
 Young-Hwan Kim  ;  Ji-Hyun Jeong  ;  Duck-Sun Ahn  ;  Seungsoo Chung 
Citation
 Biochemical and Biophysical Research Communications, Vol.484(2) : 342-347, 2017 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2017
MeSH
Abdomen ; Agmatine/pharmacology* ; Animals ; Calcium Channel Blockers/pharmacology ; Calcium Channels, N-Type/drug effects* ; Ganglia, Sympathetic/drug effects* ; Ganglia, Sympathetic/metabolism ; Hydrolysis ; Male ; Neurons/drug effects ; Neurons/metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism* ; Rats ; Rats, Sprague-Dawley ; Type C Phospholipases/metabolism*
Keywords
Agmatine ; Cav2.2 ; Imidazoline receptor ; Phosphatidylinositol 4,5-bisphosphate
Abstract
Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (ICav2.2) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited ICav2.2 in a VI manner. The agmatine-induced inhibition of the ICav2.2 current was also almost completely hindered by the blockade of the imidazoline I2 receptor (IR2), and an IR2 agonist mimicked the inhibitory effect of agmatine on ICav2.2, implying involvement of IR2. The agmatine-induced ICav2.2 inhibition was significantly hampered by the blockade of G protein or phospholipase C (PLC), but not by the pretreatment with pertussis toxin. In addition, diC8-phosphatidylinositol 4,5-bisphosphate (PIP2) dialysis nearly completely hampered agmatine-induced inhibition, which became irreversible when PIP2 resynthesis was blocked. These results suggest that in rat peripheral sympathetic neurons, agmatine-induced IR2 activation suppresses Cav2.2 channel voltage-independently, and that the PLC-dependent PIP2 hydrolysis is responsible for the agmatine-induced suppression of the Cav2.2 channel.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X17301791
DOI
10.1016/j.bbrc.2017.01.120
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
김영환(Kim, Young Hwan)
안덕선(Ahn, Duk Sun) ORCID logo https://orcid.org/0000-0001-9351-6951
정승수(Chung, Seung Soo) ORCID logo https://orcid.org/0000-0002-3119-9628
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154343
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